Sirtuin is a collective name for a group of NAD+ dependant deacetylase, which is distributed in a wide range from bacteria to eukaryote, and various sirtuins have been identified including 5 types in yeast, such as Sir2, and 7 types in human (SIRT1 to SIRT7). Sirtuins in the cells are found in cytoplasm, mitochondria, etc., and they play an important part in the living body.
Sir2 was first found as a longevity gene of yeast, and it was subsequently proven to regulate aging/lifespan in the nematode and the fruitfly. There is a report that Sir2 provides a life lengthening effect through DNA repair and recombination by preventing acetylation of histone, which has a gene-protection effect (Non-Patent Document 1). The human SIRT1, which exhibits high homology with the yeast Sir2, is known to deacetylate lysine 382 of the p53 protein, associated with aging, to thereby regulate p53 and secure an anti-aging effect (Non-Patent Document 2). It is thus expected that an activation of SIRT1 would rejuvenate cells and prevent their aging, in other words, lengthen their lifespan.
Further, it is known that the waning of the oxidative phosphorylation reaction of mitochondria and the decrease in the amount and functionality of mitochondria, caused by obesity and aging, induce metabolic syndrome and diabetes. It is expected that when deacetylation of PGC-1α is accelerated through the activation of SIRT1, PGC-1α, as a transcription cofactor, would enhance the protein expression of GLUT4 and mitochondria, provide an anti-aging effect, and thus, improve metabolic syndrome and diabetes (Non-Patent Document 3).
SIRT1 activates endothelial NO synthase (eNOS) and induces endothelium dependent vasodilation, and in an experiment in which SIRT1 was overexpressed, the age-dependent left ventricle dysfunction was regulated; hence, an activated SIRT1 is expected to prevent aging of the cardiovascular systems and aging-related diseases. Additionally, SIRT1 regulates synthesis of gelatinase MMP-9 via NK-κB. Considering that MMP-9 decomposes collagen and induces inflammation, it can be determined that an activated SIRT1 would provide an anti-aging effect and an anti-inflammatory effect of the skin (Non-Patent Document 4).
While calorie regulation and a balanced diet constitute factors for activating a sirtuin gene, plant components and synthetic agonists that activate sirtuin are also seen with expectation. It has recently been reported that a polyphenol compound “resveratrol” contained in wines, etc., is effective in activating sirtuin (Non-Patent Document 5), and the effects of intaking a resveratrol-containing supplement, such as the regulation of aging, prevention of metabolic syndrome, or improvement of diabetes, are receiving attention. However, natural resveratrol that can be used in food is limited to certain resources, such as grape skin and grape leaf, and the content is extremely low, so a natural sirtuin-activating substance of a low price that is easier to obtain than resveratrol is awaited, and a stronger sirtuin activating substance is desired (Non-Patent Document 6).
Kaempferia parviflora is a plant in the genus Kaempferia of the plant family Zingiberaceae, which is also known as black ginger, Thai ginseng, or Kra chai dahm. Black ginger is cultivated widely in Thai, its country of origin, and it has been taken commonly from old, to be used in enhancing nutrition, enhancing (sexual) energy, reducing blood glucose level, recovering physical strength, and improving the circulatory system or the digestive system. Other effects of black ginger including anti-inflammatory effect (Non-Patent Document 7), effect of improving sensitivity to cold (Patent Document 1), cAMP-phosphodiesterase activation effect (Patent Document 2), antiallergic effect (Non-Patent Document 8) are reported by recent researches. However, there is no report to date of black ginger having an effect of activating sirtuin genes.
Further, flavonoid is a type of polyphenol, and it is a collective name of a series of plant pigments that exists widely in plants, such as vegetables and fruits, and that has a basic backbone of C6—C3—C6. Flavonoid has been considered an unnecessary component until recently, but an advance in the research of the biological regulation function of food unfolded various physiological functions of flavonoid and made flavonoid one of the most popular food components.
Of the flavonoid compounds, those having many hydroxyl groups, namely, butein (3,4,2′,4′-tetrahydroxychalcone), isoliquiritigenin (4,2′,4′-trihydroxychalcone), fisetin (3,7,3′,4′-tetrahydroxyflavone), quercetin (3,5,7,3′,4′-pentahydroxyflavone), were reported as having a sirtuin activation activity, but their activity was weaker than resveratrol (Non-Patent Document 4).
Polyalkoxyflavonoid is a group of compounds that are flavonoids substituted with an alkoxy group at one or more of position 3, position 5, position 6, position 7, position 8, position 2′, position 3′ and position 4′, and a polyalkoxyflavonoid substituted by a plurality of alkoxy groups (particularly, methoxy group) is reported (Non-Patent Documents 9 and 10). Polyalkoxyflavonoid is reported to have an anti-oxidant effect, anti-inflammation effect, androgen receptor binding inhibition effect (Patent Document 3), matrix metalloproteinase generation inhibition effect (Patent Document 4), UV ray inducing prostaglandin E2 generation regulation effect (Patent Document 5), vascularization regulation effect (Patent Document 6), etc. However, no report has yet been provided concerning sirtuin activation activity of polyalkoxyflavonoid.